A collaborative team involving investigators led by the Institute of Human Virology-University of Maryland (IHV) will identify 115 pregnant women with acute HIV infection. Our long-term goal is to advance the understanding of mother-to-child transmission (MTCT) risk in women who acquired HIV infection during pregnancy. Employing a combination of rapid HIV assays and multi-stage pooled nucleic acid amplification tests, pregnant women from Nigeria will be enrolled during the window of viral antigenemia and prior to development of confirmatory antibodies positivity. This research extends the knowledge of early host-virus interaction to address the specific prevention needs within the context of the prevention of MTCT (PMTCT). We hypothesize that acute HIV infection among pregnant women is underestimated within the setting of PMTCT program and is characterized by its association with vaginal infections that are under-diagnosed during pregnancy. Maternal acute HIV infection could increase the risk of MTCT and affect viral selection compared to long-standing HIV infection. The unique HIV subtypes in Nigeria characterized predominantly by subtype G and CRF02_AG could also alter the transmission risk. To test these interlocking hypotheses, we propose to: (1) determine the incidence rate and correlates of acute HIV infection among pregnant women, (2) evaluate the associations between acute HIV infection, HIV subtypes, and mother-to-child transmission, and (3) use single genome amplification to compare the level of genetic selection present in MTCT in relations to acute and long-standing maternal HIV infection. While compelling evidences suggest the potential importance of detecting incident maternal HIV infection, remarkably little attention has been devoted to this goal. Not surprisingly, MTCT during acute HIV and its relation to the effect of antiretroviral prophylaxis has not been evaluated. This proposal will provide a unique view of secondary HIV infection (i.e. from an acutely infected index case to a susceptible individual) within the context of mother-to-child transmission and of pathogenesis including early host-virus interactions. It also tackles the issue of missed opportunity for prevention directed at pregnant women with acute infection that would otherwise be missed by conventional antibody-based testing strategies. Lastly, very early recognition may allow for HIV treatment that could alter the natural history of the disease. All in all, this proposal will permit exciting epidemiological, clinical, and public health research opportunities.